North Park University

The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.

Structural equation modeling is used to estimate the mediating effects of affective, continuance, and normative commitment on the relationship between job satisfaction and intent to leave. Several competing configurational models are tested to determine whether the best fitting model is one whereby multidimensional commitment fully mediates, partially mediates, or does not mediate the relationship between job satisfaction and intent to leave. The results suggest that contrary to Meyer and Allen's (1991) fully mediated three-component model of organizational commitment, a partially mediated model fits the data best for this study. Copyright © 2000 John Wiley & Sons, Ltd.

We propose and apply a new approach for analyzing the effects of fiscal policy using vector autoregressions.Specifically, we use sign restrictions to identify a government revenue shock as well as a government spending shock, while controlling for a generic business cycle shock and a monetary policy shock.We explicitly allow for the possibility of announcement effects, i.e., that a current fiscal policy shock changes fiscal policy variables in the future, but not at present.We construct the impulse responses to three linear combinations of these fiscal shocks, corresponding to the three scenarios of deficit-spending, deficit-financed tax cuts and a balanced budget spending expansion.We apply the method to US quarterly data from 1955-2000.We find that deficit-financed tax cuts work best among these three scenarios to improve GDP, with a maximal present value multiplier of five dollars of total additional GDP per each dollar of the total cut in government revenue five years after the shock.

To assess the effect of “metacognitive” instruction on reading comprehension, 20 studies, with a total student population of 1,553, were compiled and quantitatively synthesized. For 115 effect sizes, or contrasts of experimental and control groups' performance, the mean effect size was .71, which indicates a substantial effect. In this compilation of studies, metacognitive instruction was found particularly effective for junior high students (seventh and eighth grades). Among the metacognitive skills, awareness of textual inconsistency and the use of self-questioning as both a monitoring and a regulating strategy were most effective. Reinforcement was the most effective teaching strategy.

The types and severity of stressors and methods of coping with stress were assessed for 35 patients on hemodialysis. Coping was measured with a tested scale and stress was evaluated with a scale developed for the study. Test-retest reliability of the stressor scale was satisfactory (rs = .71). Results indicated that stressors experienced by the hemodialysis patient can be measured with an objective tool; psychosocial stressors have an impact equal to that of physiological stressors. Fluid restriction was ranked as the highest psychosocial stressor and the top physiological stressors were muscle cramps and fatigue. Patients on dialysis for one to three years indicated the greatest amount of stress. Patients used problem-oriented coping methods significantly more than affective-oriented methods (t [34] = 7.06), p greater than .001). Optimism and controlling the situation were the two most common coping methods, and putting the problem out of one's mind and blaming someone else were the least important coping tools.

Using nationally representative data on consumption, we show that Blacks and Hispanics devote larger shares of their expenditure bundles to visible goods (clothing, jewelry, and cars) than do comparable Whites.We demonstrate that these differences exist among virtually all sub-populations, that they are relatively constant over time, and that they are economically large.While racial differences in utility preference parameters might account for a portion of these consumption differences, we emphasize instead a model of status seeking in which conspicuous consumption is used to reflect a household's economic position relative to a reference group.Using merged data on race and state level income, we demonstrate that a key prediction of our model --that visible consumption should be declining in mean reference group income --is strongly borne out in the data separately for each racial group.Moreover, we show that accounting for differences in reference group income characteristics explains most of the racial difference in visible consumption.We conclude with an assessment of the role of conspicuous consumption in explaining lower spending by racial minorities on items likes health and education, as well as their lower rates of wealth accumulation.

We thank Dan Reichgott

In most of the world, people have regular exposure to multiple accents. Therefore, learning to quickly process accented speech is a prerequisite to successful communication. In this paper, we examine work on the perception of accented speech across the lifespan, from early infancy to late adulthood. Unfamiliar accents initially impair linguistic processing by infants, children, younger adults, and older adults, but listeners of all ages come to adapt to accented speech. Emergent research also goes beyond these perceptual abilities, by assessing links with production and the relative contributions of linguistic knowledge and general cognitive skills. We conclude by underlining points of convergence across ages, and the gaps left to face in future work.

Infection with human immunodeficiency virus (HIV) may cause viral antigenemia, detected primarily as p24 viral core protein. Among 16 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex studied serially, 12 had or developed antigenemia ranging from 16 to 3006 pg/mL in plasma. The level could be categorized as high (greater than 100 pg/mL) or low (15 to 65 pg/mL). Three patients with anti-p24 antibody had no antigenemia. Zidovudine (AZT), 200 or 250 mg every 4 hours, reduced antigenemia by about 90%; other regimens were less effective. Leukocyte cultures were positive for HIV from patients with antigenemia, and in one third of samples in the absence of antigenemia. High levels of antigenemia correlated with symptoms, CD4 cell count, and prognosis. Drug toxicity requiring a lower dose was followed by increased antigenemia, recurrent symptoms, and decreased CD4 cells, suggesting lymphocyte toxicity. Monitoring antigenemia can be useful in evaluating patients with HIV infection and in evaluating the effect of antiviral chemotherapy.

BACKGROUND: Cocaine abuse has been implicated as a cause of death due to sudden cardiac arrest. METHODS AND RESULTS: We examined the hemodynamic and electrophysiological effects of cocaine administered as a series of 5-mg/kg i.v. boluses coupled with a continuous infusion in anesthetized dogs. Sodium bicarbonate (50 meq i.v.) was administered as a potential antidote in 11 of 15 dogs, and intravenous 5% dextrose was given in the remaining four. In a dose-dependent fashion, cocaine significantly decreased blood pressure, coronary blood flow, and cardiac output; increased PR, QRS, QT, and QTc intervals and sinus cycle length; and increased ventricular effective refractory period and dispersion of ventricular refractoriness. No afterdepolarizations were noted in the monophasic action potential recording. Nonsustained monomorphic ventricular tachycardia occurred spontaneously in two dogs, and sustained ventricular tachycardia could be induced by programmed stimulation at the end of the dosing protocol in five of 11 animals. Sodium bicarbonate promptly decreased cocaine-induced QRS prolongation to nearly that measured at baseline but had no effect on the other electrocardiographic or hemodynamic variables. In one dog, sodium bicarbonate administration was associated with reversion of ventricular tachycardia to sinus rhythm. CONCLUSIONS: We conclude that high-dose cocaine possesses negative inotropic and potent type I electrophysiological effects. Sodium bicarbonate selectively reversed cocaine-induced QRS prolongation and may be a useful treatment of ventricular arrhythmias associated with slowed ventricular conduction in the setting of cocaine overdose.

Abstract Affect plays a central role in human experience, providing the ongoing hedonic tone that colors the everyday lives of individuals. Not surprisingly, therefore, affect occupies an equally prominent role in the psychological and social science literature. As such, a number of different approaches exist for assessing mood and emotion. This chapter focuses on outlining and describing a variety of self-report measures that are available to affect researchers. In outlining the available means for measuring affect, we must address two central issues. First, we must be clear about the definitions of affect, emotion, and mood that will be used within this chapter. The constructs of mood and emotion are similar in that they both refer to feeling states that can be broadly characterized as pleasant or unpleasant (i.e., as positive or negative) and that reflect what is happening within the organism (Parkinson, Totterdell, Brinner, & Reynolds, 1996). It is also widely believed that they contain some common components and are controlled by similar processes (Clark & Watson, 1999; Parkinson et al., 1996).

A new computational approach to the problem of limit analysis with quadratic yield condition is developed and tested. The problem is solved using the exact convex yield condition and the general case of unbounded yield set, corresponding to unrestricted hydrostatic pressure, is treated. The discretization by the finite element method is based on an analysis of the duality between the static principle and the kinematic principle of limit analysis. Also the solution method for the discrete optimization problem is new and exploits this duality. The method simultaneously computes approximations to the fields of stresses and flow in the collapse state. The software used for the optimization problem is independent of continuum mechanics, but has been developed with applications in limit analysis as a primary objective. The efficiency and accuracy of the method for large problems is demonstrated by solving a classical problem in the plane strain model: approximately 90 000 finite element nodes with 3 stress components and 2 velocity components at each node. In two space dimensions this may be overkill, but it shows that we are able to solve problems in three space dimensions. Copyright © 1999 John Wiley & Sons, Ltd.

Synthetic biology offers opportunities for experiential educational activities at the intersection of the life sciences, engineering, and design. However, implementation of hands-on biology activities in classrooms is challenging because of the need for specialized equipment and expertise to grow living cells. We present BioBits™ Bright, a shelf-stable, just-add-water synthetic biology education kit with easy visual outputs enabled by expression of fluorescent proteins in freeze-dried, cell-free reactions. We introduce activities and supporting curricula for teaching the central dogma, tunable protein expression, and design-build-test cycles and report data generated by K-12 teachers and students. We also develop inexpensive incubators and imagers, resulting in a comprehensive kit costing

This paper summarizes five facts that have emerged from the recent literature on consumption behavior during retirement.Collectively, the recent literature has shown that there is no puzzle with respect to the spending patterns of most households as they transition into retirement.In particular, the literature has shown that there is substantial heterogeneity in spending changes at retirement across consumption categories.The declines in spending during retirement for the average household are limited to the categories of food and work related expenses.Spending in nearly all other categories of non-durable expenditure remains constant or increases.Moreover, even though food spending declines during retirement, actual food intake remains constant.The literature also shows that there is substantial heterogeneity across households in the change in expenditure associated with retirement.Much of this heterogeneity, however, can be explained by households involuntarily retiring due to deteriorating health.Overall, the literature shows that the standard model of lifecycle consumption augmented with home production and uncertain health shocks does well in explaining the consumption patterns of most households as they transition into retirement.

The organic constituents of exhaled human breath are representative of blood-borne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds (VOCs), sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. To exploit these advantages, we have developed the "single breath canister" (SBC) technique, a simple direct collection method for individual alveolar breath samples, and adapted conventional gas chromatography-mass spectrometry analytical methods for trace-concentration VOC analysis. The focus of this paper is to describe briefly the techniques for making VOC measurements in breath, to present some specific applications for which these methods are relevant, and to demonstrate how to estimate exposure to example VOCs on the basis of breath elimination. We present data from three different exposure scenarios: (a) vinyl chloride and cis-1,2-dichloroethene from showering with contaminated water from a private well, (b) chloroform and bromodichloromethane from high-intensity swimming in chlorinated pool water, and (c) trichloroethene from a controlled exposure chamber experiment. In all cases, for all subjects, the experiment is the same: preexposure breath measurement, exposure to halogenated VOC, and a postexposure time-dependent series of breath measurements. Data are presented only to demonstrate the use of the method and how to interpret the analytical results.

Musculoskeletal performance assessment is critical in the analysis of physical training programs in order to prioritize goals for decreasing injury risk and focusing performance goals. Abdominal endurance as part of this analysis is often assessed with techniques that have validity that has been debated in literature. The purpose of this study was to develop normative sex- and athlete-specific percentiles for a trunk stabilization and muscular endurance by using a prone forearm plank test in college-aged students. A second purpose of this study was to investigate the effect of habitual physical activity and the reason for test termination. There were 471 participants (means ± SE; males: n = 194, age 20.4 ± 0.2 years, body height 179.4 ± 0.5 cm, body mass 81.1 ± 1.2 kg; females: n = 277, age 20.2 ± 0.2 years, body height 165.7 ± 0.4 cm, body mass 63.9 ± 0.7 kg) who performed this test to volitional or technique failure. Males produced significantly higher test durations than females (means ± SD; 124 ± 72 seconds vs. 83 ± 63 seconds) and athletes produced significantly longer test durations than non-athletes (123 ± 69 s vs. 83 ± 63 s) but no interaction effects were seen in the variables of sex and athletic status. The activity level was found to have a threshold of influence (>3 times/week) on abdominal endurance that is dose-specific where greater than 5 times/week showed the greatest influence. The fatigue of the abdominals was the termination reason producing the lowest test duration and there was no sex effect on reason for test termination. These normative percentiles for abdominal endurance suggest that the abdominal plank test can now be used as an alternative to other abdominal assessments in college students, but further investigation is warranted prior to confirmation and generalization to other populations.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare, lethal disease generally seen in young male patients with inflammatory bowel disease. The study of biologic and immunomodulator naive patients in Crohn's disease (SONIC), advocates combining infliximab with an immunomodulator in moderate-to-severe Crohn's disease. Unfortunately, combined immunosuppression increases risk for HSTCL. We herein review all cases of HSTCL reported to the Food and Drug Administration (FDA) in patients receiving TNF-α inhibitors. METHODS: Individual reports from the FDA Adverse Event Reporting System database for lymphomas from the biological agents - infliximab, adalimumab, certolizumab, natalizumab, and etanercept were downloaded and analyzed with Microsoft Access. Full reports for all identified HSTCL cases were obtained from the FDA. RESULTS: Twenty-five cases of HSTCL were identified. Twenty-two (88%) patients had inflammatory bowel disease and three had rheumatoid arthritis. Four cases (16%) were in women and four patients were above 65 years of age. Twenty-four cases (96%) also received an immunomodulator (azathioprine, 6-mercaptopurine, or methotrexate). Two patients received adalimumab alone. CONCLUSION: HSTCL is no longer restricted to the previously identified risk group of young male patients, but can also occur in patients with rheumatoid arthritis, females and older adults receiving TNF-α inhibitors and immunomodulators. Improved disease outcomes using combination therapy should be tempered by the risk of developing HSTCL.

BACKGROUND & AIMS: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. METHODS: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans. RESULTS: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis. CONCLUSIONS: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH. IMPACT AND IMPLICATIONS: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis.